Year: 2014
Type: article
Abstract: Allergic asthma is a heterogeneous inflammatory disease of the airway that affects millions of people worldwide.A subgroup of patients with severe asthma often has persistent symptoms and frequent exacerbations, leading to poor disease control and considerable morbidity.Accumulating clinical evidence suggests that airway eosinophilic inflammation is associated with a subphenotype of asthma that is prone to become exacerbated; however, the underlying immunological and molecular mechanisms that preferentially drive the eosinophilic phenotype of severe asthma remain elusive.The first section of this dissertation investigates the relative roles of CD4 + Th2, CD4 + Th17 cells and type 2 innate lymphoid cells (ILC2s) during repeated Ag re-challenge induced chronic murine allergic airway disease with prominent eosinophilic inflammation.We observed that the increase in airway eosinophils was positively associated with the number of repeated intranasal OVA Ag re-challenges, which preferentially drive the OVA Ag-specific humoral and cellular Th2 immune response.Using IL-4-GFP and IL-17-GFP reporter mice (both in BALB/c background), we found that, although both OVA Ag-specific CD4 + Th2 and Th17 cells were induced in the lung of mice that developed acute murine allergic airway disease, repeated Ag rechallenge preferentially drove the increase of lung OVA Ag-specific CD4 + Th2, not CD4 + Th17, cell numbers.Notably, the increased number of lung CD4 + Th2 cells resulted in enhanced IL-13 production by lung ILC2s in response to IL-25 and IL-33 stimulation, which decreased considerably in mice after CD4 + T cell ablation.Reciprocally, ILC2s could facilitate Ag-specific CD4 + Th2 cells to mediate the exacerbation of murine allergic airway disease by promoting Agspecific type 2 cytokine production.iii I would like to thank everyone in the immunology graduate program and division of allergy and immunology, for providing such an encouraging environment for me to grow from a student who knows little about immunology to a real immunologist.First and foremost, I would like to sincerely thank my mentor Dr. Yui-Hsi Wang for his tremendous patience in teaching me all the skills he knows to become an immunologist.He spends so much time with me discussing not only about how to do good science but also about life, most likely more than the time he spent with his daughter.His passion, perseverance and commitment in doing great science will continue to inspire me for the rest of my life.Secondly, I would like to express my deep gratitude to members of my thesis committee, Dr.
Author: Bo Liu
Institution: University of Cincinnati
Language: English
Topic: IL-33, ST2, and ILC Pathways
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2603118848